Disclosures" Controversies in women’s health 2016: Recognition and treatment of common disorders I have no conflicts of interest to disclose." of the skin" " I may discuss off-label use of treatments for cutaneous disease." Kanade Shinkai, MD PhD! Associate Professor of Clinical Dermatology! University of California, San Francisco" A preview" • Fictional patient" " Acne" • Series of dermatology visits" " • Numerous concerns" "• Acne" "• Drug eruptions" "• Skin cancer" Acne “emergency”" Acne pearls for adult female patients" • Many adult females fail standard acne therapy" "- 82% fail multiple systemic antibiotics" "- 1/3 fail systemic isotretinoin" "" • Systemic antibiotics (short-term use only)" "- indicated for nodulocystic acne, truncal acne" "- may require 3 months for truncal lesions" "- works faster than hormonal therapy (2-3 weeks)" Hormonal treatment can be highly-effective for acne in this population" Hormonal therapy versus antibiotics" How do OCPs work?" • Estrogen provides the most benefit" " • Actions:" "1. Stimulates SHBG synthesis (liver): " " "- decrease free testosterone, DHEA-S" "2. Inhibit 5α-reductase" • 226 publications, 32 RCT" "3. Decrease production of ovarian, adrenal androgens" • Antibiotics superior @ 3 months" " • Equivalent to systemic antibiotics @ 6 months" • Lesion count reduction: 40-70%" " " " " " Koo EB et al (2014) JAAD 71:450-459" Koo EB et al (2014) JAAD 71:450-459" Haider A and JC Shaw (2004) JAMA 292:726-735" My acne patient didn’t respond to OCP. ! Which OCP is best?" Will adding spironolactone help?" • FDA-approved for acne: no superiority data" "-Ortho Tri-Cyclen: norgestimate + ethinyl estradiol/ EE" Effective: non-FDA approved, no placebo-controlled trials" " " "-EstroStep: norethindrone acetate + EE "" • spironolactone alone or with OCP (50-200mg/day)" " " "-Yaz: drospirenone + EE" • 33-85% reduction in acne" " " "- dosing 50-100mg/day: 33% improvement" "• High estrogen, low androgenic (progesterone) activity" " "- 100mg + drospirenone: 85% improvement" "-norgestimate, desogestrel (3rd gen progestins)" " " "-drosperinone (4th gen progestin)" " "-nomegestrel acetate (NOMAC)" Brown J et al (2009) Cochrane Database of Sys Rev 2:CD000194" Haider A and JC Shaw (2004) JAMA 292:726-735" Arowojolu AO et al (2012) Cochrane Database Syst Rev, 6:CD004425" Shaw JC (2000) JAAD 43:498-502" Haider A and JC Shaw (2004) JAMA 292:726-735" Krunic A et al (2008) JAAD 58:60-2" Spironolactone: safe, has side effects" Spironolactone: the scare over potassium" • 8 year safety study in acne: no serious complications" • Main side effects: "menstrual irregularities (22%) " " ""breast tenderness (17%) " " ""fatigue (15%) " " ""headache (13%)" • monotherapy only at low doses, select patients" • hyperkalemia (minimal rise in K+ in 13%, no sequelae) " 425 mg" 366 mg" 600 mg" 30 mg" 235 mg" • blood pressure reduction: mean 5mmHg SBP, 2.6mmHg DBP" " " " " " • TERATOGEN: Category C/D" " " RDA K+: 4700" mg" " " • Black box warning: benign tumors in animal studies" Low usefulness of screening in healthy " Haider A and JC Shaw (2004) JAMA 292:726-735 " "" young acne patients" Shaw JC (2000) JAAD 43:498-502" " Shaw JC, White LE (2002) J Cut Med Surg 6:541-545 "" " George R et al (2008) Sem Cut Med Surg 28:188-196" Plovanich M et al (2015) JAMA Derm, 151:941-944" " " " " " Do other forms of contraception help acne?" When should I worry about a hormonal disorder?" Vaginal ring: minimal data on efficacy with acne" • Hirsutism, acanthosis nigricans" "• etonorgestrel (derivative of 3rd gen progestin)" " "• Cochrane review (2010): Nuva-users have less acne" • Oligomenorrhea (<8 per year) or amenorrhea" "• adverse effects: intermediate clotting risk" " " • Virilization: "Deepening voice" Intrauterine" devices: caution" " " "Clitoromegaly" "• levonorgestrel (2nd gen progestin)" " " "Increased muscle mass" "• hormone-eluting IUDs may worsen acne (Cutis 2008)" " " "Decreased breast size" "• plasma concentration @ 1 month: 50% of Norplant" " " """"" " Virilization"" = sign of androgen-secreting tumor" " " Ilse JR et al (2008) Cutis, 82: 158" Azziz R et al (2004) J Clin Endo Metab, 89:453-462" Lopez LM et al (2010) Cochrane Review, CD003552" " Escobar-Morreale H et al (2012) Hum Reprod Update, 18:146-170" Chi IC (1991) Contraception, 44: 573--588" JC Harper (2008) J Drugs Derm 7: 527-530" Lolis MS et al (2009) Med Clin N Am 93:1161-1181 "" " " " Hyperandrogenism workup: results" Polycystic Ovary Syndrome (PCOS)" Rotterdam criteria (2003): 2 of 3" PCOS Idiopathic Idiopathic NCCAH Tumors Misc "• oligomenorrhea (< 8 per year)" HA Hirsutism "• serum or clinical hyperandrogenism" "• ultrasound (+) polycystic ovaries" 71% 15% 10% 3% 0.3% 0.7% • Prevalence: 5-10%" • Heterogeneous presentation" " PCOS is #1 cause of androgen excess" Tumors, hormonal disorders are very rare" " " Escobar-Morreale H et al (2012) Human Repro Update, 18:146-170" Stein & Leventhal (1935) Am J Obstet Gynecol, 29:181-191 "" Rotterdam ESHRE/ASRM-sponsored PCOS Consensus Workshop Group (2004) Human Reproduc. 19:41-47 "" " Cutaneous signs of PCOS" Hirsutism: best skin sign of hyperandrogenism" Pearls:" • look beyond the face (trunk, proximal extremities)" " • spironolactone 100 qD- BID has best efficacy" Cross-sectional UCSF study" 401 women suspected of having PCOS " Comprehensive skin exam by dermatologist" 92% of patients with PCOS had skin finding "" Schmidt T et al (2015) JAMA Derm, Dec 23:1-8! " Schmidt TH, Shinkai K (2015) JAAD 73:672-690" " " Androgenic alopecia: poor skin sign of Diagnostic workup for PCOS" hyperandrogenism" Step 1:" Step 2:" When? Endocrine" Metabolic" Pearls:" " " • Testosterone (free, total)" • BMI" • frontal hairline is " " preserved" • 17-hydroxyprogesterone" • Blood pressure" • total baldness is rare in • trans-vaginal ultrasound" • Fasting lipid panel" women" " • Fasting insulin, glucose" " •" DHEA-S" • 2 hour glucose challenge" • topical minoxidil 5% daily" "• TSH" • HgbA1c" • 6-12 months" • prolactin" • ALT" • androstenedione! " • LH: FSH (>3 in 95% PCOS)! " Dizon M, Schmidt TH, Shinkai K (2016) Cutis, 98:11-13" Schmidt TH, Shinkai K (2015) JAAD 73:672-690" " " " " Back to our acne patient:! Drug eruptions" 10 days after starting doxycycline, your patient develops an itchy generalized maculopapular rash" Morbilliform drug eruption" • common" • erythematous macules, papules " (can be confluent)" • pruritus" • no systemic symptoms " • begins in 1st or 2nd week" • treatment: " "-D/C med if severe" "-symptomatic treatment: " " hydroxyzine, topical steroids" " When do the symptoms subside? " Drug eruptions: ! Up to 1 week" when to worry" Minimal systemic symptoms" Systemic involvement" Morbilliform drug eruption" DRESS" " AGEP" " Stevens-Johnson (SJS)" " Toxic epidermal necrolysis" " (TEN)" Simple" Complex" Potentially life threatening" Require systemic immunosuppression" Drug eruptions: ! Signs of a serious drug eruption:" timing of onset can be helpful" • Mucosal involvement (ie, oral ulcerations)" Minimal systemic symptoms" Systemic involvement" • Erythroderma" • Skin pain" Morbilliform drug eruption" DRESS" 2-6 weeks" • Target lesions" 5-14" days" AGEP" 1-4 days" • Bullous lesions" " Stevens-Johnson (SJS)" • Denudation (skin falling off in sheets)" " Toxic epidermal necrolysis" • Pustules" " (TEN) "5-20 days" • Facial swelling, anasarca" Simple" Complex" • Fever" • Internal organ involvement: liver, kidney > lung, cardiac" Potentially life threatening" Require systemic immunosuppression" Target lesions: Stevens Johnson Syndrome (SJS)" Mucosal involvement: SJS/ TEN" Facial swelling: drug-induced hypersensitivity Bullous lesions, denudation, pain: TEN" syndrome or DRESS! Also: eosinophilia, transaminitis, renal failure" Widespread pustules: acute generalized Drug eruption pearls" exanthematous pustulosis (AGEP)! Also: eosinophilia, renal failure" Look for cutaneous signs of a potentially-fatal drug eruption" " Consider ordering labs if you are not sure " "" " Lab order! What you are looking for! Drug eruption! CBC with differential" Eosinophilia" Any drug hypersensitivity" (may be slightly increased in simple drug eruption)" ALT, AST" Transaminitis" Drug-induced hypersensitivity syndrome" BUN, Cr" Acute renal failure" Drug-induced hypersensitivity syndrome, AGEP" Patient returns with a changing mole" “Spots,” skin cancers, melanoma" Melanoma" Melanoma" A " = "asymmetry" " B = "irregular border" " C" = "color" " D" = "diameter >6mm" " E " = "evolution" " complete biopsy" " Melanoma: initial evaluation" D/dx of a pigmented lesion?" •$ Prognosis is DEPENDENT on the depth of Mole/ nevus" lesion (Breslow’s depth)" " –$< 1mm thickness is low risk" –$> 1mm consider sentinel lymph node biopsy" •$ If melanoma is on the differential, complete excision or full thickness incisional biopsy is indicated" Seborrheic keratoses" Seborrheic keratoses" • benign keratinocytic papules" " • trunk, extremities > face" " • do not progress to malignancy" " • stuck-on tan, ovoid papule/ plaque" " • sometimes symptomatic" " Solar lentigo/lentigines" Cherry angioma (d/dx: Spitz nevus, melanoma)" Pigmented, flat, even color" Irregular borders" Multiple, 1-2 mm in size" Sun exposed areas" Age 30+" " " Actinic purpura, actinic keratoses" Non-melanoma skin cancer" What about this new skin lesion?" Basal cell carcinoma" • pearly papule or plaque " " - central ulceration" " - telangiectasia" " • slow growing" " • invade locally" " • Rx: surgical excision" " "curettage" " "superficial -> topical" BCC can be pigmented" Squamous cell carcinoma" • scaly erythematous plaque